Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Electrophoretic profiles of the molecular weight distributions of fibrinogen derivatives in blood provide a tool for combined assessment of coagulation and fibrinolysis in the course of vascular disease. Profiles obtained in studies on an experimental model of hypertension and in humans with occlusive vascular disease are discussed. In the experimental studies elevations in the level of cross-linked dimers provided a more reliable means for predicting development of malignant hypertension than did many other criteria, especially near the outset when blood pressure changed to similar degrees in rats with malignant and benign hypertension. Similarly, we find that levels of dimeric and occasionally trimeric forms of fibrinogen are more prominently elevated than degraded forms of fibrinogen in patients with occlusive vascular disease.
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PMID:Malignant hypertension, fibrinoid deposition, and fibrinogen electrophoresis. 266 31

Fibronectin (FN) is a dimeric glycoprotein found in the extracellular matrix of most tissues that serves as a bridge between cells and the interstitial collagen meshwork and influences diverse processes including cell growth, adhesion, migration, and wound repair. Multiple FN forms arise by the alternative splicing of a primary transcript originating from a single gene. The spatial and temporal alterations in FN expression in the myocardium has been studied in models of cardiac growth in vivo such as fetal development, and hypertrophy secondary to pressure overload. This review focuses on the differential expression of FN isoforms that are observed in different models of cardiac growth. Using a combination of qualitative and quantitative analyses it is shown that in the rat myocardium: (1) the FN phenotype is developmentally regulated, (2) the re-expression of the fetal FN isoforms is observed in different models of cardiac hypertrophy secondary to a sudden or progressive hypertension and (3) the changes in cardiac FN expression affect mostly the coronary artery smooth muscle cells.
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PMID:Fibronectin expression during physiological and pathological cardiac growth. 756 10

Fibronectin is a dimeric glycoprotein found in the extracellular matrix of most tissues, which can influence processes, including cell growth, adhesion and migration. Fibronectin synthesis has been shown to be overexpressed in hypertension. However, the respective effects of humoral factors, including angiotensin II, versus mechanical factors in vascular remodeling have not yet been clarified. To study fibronectin de novo synthesis in the arterial wall, we have developed a new model for organ culture of rabbit thoracic aorta. Arteries held at their in vivo length were incubated and perfused (40 ml/min) in DME medium containing antibiotics, supplemented with 20% fetal calf serum or with 5% bovine serum albumin. In a series of experiments, angiotensin II (10(-6) M) and indomethacin (10(-5) M) were added to culture media. Vessels were pressurized at 0, 80 or 150 mmHg, and kept for 3 days in incubator at 37 degrees C under 5% CO2. De novo synthesis of fibronectin was detected by immunofluorescence using anti-cellular fibronectin antibodies (1/200). In the absence of angiotensin II and serum, fibronectin was expressed in the sub-endothelium at 80 mmHg, and in the inner media at 150 mmHg. In the presence of serum, fibronectin expression was increased by the high pressure. When angiotensin II was added, a gradient of fibronectin became apparent in the inner media at 80 mmHg with a marked expression at the luminal side. Angiotensin II markedly enhanced fibronectin expression at 150 mmHg, the protein being detected in almost the whole media. Our results indicate that both angiotensin II and transmural pressure can induce fibronectin expression in the arterial wall, and both act synergically.
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PMID:[Effects of angiotensin II and pressure on cellular fibronectin in the vascular wall in organotypic culture]. 775 79

Fibronectin (FN) is a dimeric glycoprotein found in the extracellular matrix (ECM) of most tissues and serves as a bridge between cells and the interstitial collagen meshwork. It also influences diverse processes including cell growth, adhesion, migration, and wound repair. Multiple FN forms arise by the alternative splicing of a primary transcript originating from a single gene. The spatial and temporal alterations in FN expression in the cardiovascular system have been studied in vitro in cell culture and in vivo during fetal development, hypertrophy, infarction, arterial injury and aging. This review describes characteristics of FN expression in cardiovascular system: 1. the FN phenotype is regulated during development. A high FN mRNA level is related to an early cardiac organogenesis and a progressive decrease that begins at the fetal stage and continues through senescence. During cardiac ontogeny, there is a linear correlation between total FN mRNA accumulation and the relative amounts of FN-EIIIA and EIIIB RNA. This correlation is absent during cardiac growth in the adult. 2. A differential reexpression of the FN isoforms is observed in both myocardium and aorta in different models of hypertension or infarction but with different threshold and time course. Changes in total FN mRNA levels in hypertensive models vary depending on the authors. Nevertheless the differences in the expression of the fetal forms of FN mRNA observed among the various models of hypertension-induced hypertrophy indicate that the process of FN pre-mRNA splicing in the adult myocardium is specifically regulated and depends on the pathological situations and the type of cell.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fibronectin expression in the cardiovascular system. 777 63

Human placenta expresses subunit messenger RNAs for synthesizing inhibin A and B. Experimental studies have shown an effect of inhibins on placental hormone secretion, but an endocrine function is suggested by the high levels in maternal circulation. Although information is available on the changes of inhibin A in serum of healthy pregnant women, data on inhibin B levels are limited to early gestation. The aim of the present study was to investigate the changes of inhibin B levels in maternal circulation in healthy pregnant women throughout gestation, and to evaluate whether early pregnancy disturbances or gestational diseases are characterized by abnormal inhibin B levels. The protocol included various groups of pregnant women. A longitudinal evaluation of serum inhibin B levels was done at specific intervals (8-12, 13-18, 19-24, 25-28, 29-33, and 34-40 weeks) in the following groups: 1) healthy pregnant women (n = 13); 2) women at risk of hypertension who did not develop hypertension (n = 8); and 3) women with chronic hypertension (n = 13). In women in group 1, a blood sample was also obtained in the postpartum period (12, 24, and 48 h after delivery). Other pregnant women with abnormal bleeding in the first trimester were studied; they were subdivided into women with ongoing pregnancy (n = 12); and women with miscarriage (n = 22); a control group of healthy pregnant women at the same gestational age was also included (n = 18). A final group of women with gestational diseases (n = 34) was included in the study and included women with: 1) pregnancy-induced hypertension (n = 10); 2) preeclampsia (n = 17); and 3) intrauterine fetal growth retardation (n = 7). A group of healthy nonpregnant women (n = 9) was used as controls, and a blood specimen was collected during both the early- to midfollicular and midluteal phases of the menstrual cycle. Serum dimeric inhibin B levels were measured by using a double-antibody enzyme-linked immunoadsorbent assay. Early gestation inhibin B levels were similar to those of nonpregnant controls and showed a significant rise during the third trimester (P < 0.01). The highest maternal serum inhibin B levels were found at term (P < 0.01). Values significantly returned to control levels within 12-48 h (P < 0.01) after placental delivery. Women at risk of hypertension showed a similar gestational-related increase of inhibin B levels during the third trimester, without any significant difference when compared with healthy women. Women with chronic hypertension showed significantly lower levels at term (P < 0.01). Women with pregnancy-induced hypertension or preeclampsia, or who were carrying a fetus with intrauterine growth retardation showed serum inhibin B levels during the third trimester of gestation consistently lower than in control healthy women at the same gestational age (P < 0.001, mean +/- SEM). Maternal serum inhibin B levels in women with early pregnancy bleeding or miscarriage were similar to those of healthy pregnant women at the same gestational age, independent from the outcome of gestation. The present study showed that maternal serum inhibin B levels increase in the last trimester of normal pregnancy, with low levels in women with hypertensive disturbances or intrauterine growth retardation.
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PMID:Changes of dimeric inhibin B levels in maternal serum throughout healthy gestation and in women with gestational diseases. 928 32

Dietary fatty acids specifically modulate the onset and progression of various diseases, including cancer, atherogenesis, hyperlipidaemia, insulin resistances and hypertension, as well as blood coagulability and fibrinolytic defects; their effects depend on their chain length and degree of saturation. Hepatocyte nuclear factor-4alpha (HNF-4alpha) is an orphan transcription factor of the superfamily of nuclear receptors and controls the expression of genes that govern the pathogenesis and course of some of these diseases. Here we show that long-chain fatty acids directly modulate the transcriptional activity of HNF-4alpha by binding as their acyl-CoA thioesters to the ligand-binding domain of HNF-4alpha. This binding may shift the oligomeric-dimeric equilibrium of HNF-4alpha or may modulate the affinity of HNF-4alpha for its cognate promoter element, resulting in either activation or inhibition of HNF-4alpha transcriptional activity as a function of chain length and the degree of saturation of the fatty acyl-CoA ligands. In addition to their roles as substrates to yield energy, as an energy store, or as constituents of membrane phospholipids, dietary fatty acids may affect the course of a disease by modulating the expression of HNF-4alpha-controlled genes.
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PMID:Fatty acyl-CoA thioesters are ligands of hepatic nuclear factor-4alpha. 954 58

Inhibin-related proteins are involved in the control of the feto-maternal communication required to maintain pregnancy. Human placenta, decidua, and fetal membranes are the major sites of production and secretion of activin A, inhibin A and inhibin B in maternal serum, amniotic fluid, and cord blood. The availability of suitable assays developed in the last years has enabled the measurement of inhibins and activin A in their dimeric forms, in order to investigate their role in physiological conditions of pregnancy. The studies conducted on inhibin-related proteins and human pregnancy suggested the possibility of an involvement of inhibin A and activin A in the pathogenesis of gestational diseases. In fact, several lines of evidence underline the potential role and the clinical usefulness of inhibin-related proteins measurement in the diagnosis, prevention, prognosis and follow-up of different gestational pathologies such as early pregnancy viability, Down's syndrome, fetal demise, pre-eclampsia, pregnancy-induced hypertension, preterm delivery and intrauterine growth restriction. The measurement of inhibin A and activin A into the biological fluids of pregnancy will offer in the future, further possibilities in the early diagnosis, prediction, and monitoring diseases of pregnancy.
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PMID:Changes in inhibins and activin secretion in healthy and pathological pregnancies. 1145 81

Activin A (beta A beta A) and inhibin A (alpha beta A) are dimeric glycoproteins secreted from early to term pregnancy in the maternal circulation. They circulate in higher amounts in women with gestational hypertension and/or pre-eclampsia, the most important gestational diseases also causing fetal growth restriction (FGR). Since no data are available in patients with pre-eclampsia and superimposed FGR, by using two-site immunoassays we evaluated serum activin A and inhibin A levels in serum samples collected from: healthy normotensive pregnant controls (n = 42); and women with pre-eclampsia with (n = 19) or without superimposed FGR (n = 21). In addition, by quantitative reverse transcriptase-polymerase chain reaction the changes of alpha- and beta A-subunit mRNA expression in placentas collected from healthy controls (n = 7) and pre-eclamptic pregnancies with (n = 6) or without (n = 6) superimposed FGR was also investigated. Activin A and inhibin A serum levels were significantly higher in pre-eclampsia, and the presence of FGR did not significantly modify these concentrations. Similarly, inhibin-subunit mRNA levels in placentas from pre-eclampsia were significantly higher than in controls, and FGR did not significantly affect this expression. The present data suggest that the increased placental expression of inhibin subunit mRNAs is part of the mechanism leading to increased serum activin A and inhibin A levels.
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PMID:Pre-eclampsia with fetal growth restriction: placental and serum activin A and inhibin A levels. 1258 30

Angiogenesis is important in the growth and progression of solid tumours. The main pro-angiogenic factor, namely vascular endothelial growth factor (VEGF), also known as vascular permeability factor, is a potent angiogenic cytokine that induces mitosis and also regulates the permeability of endothelial cells. The soluble isoform of VEGF is a dimeric glycoprotein of 36-46 kDa, induced by hypoxia and oncogenic mutation and it binds to two specific tyrosine-kinase receptors: VEGF-1 (flt-1) and VEGF-2 (KDR/flk1). An increase in VEGF expression in tumour tissue or some blood compartments (i.e. serum or plasma) has been found in solid and haematological malignancies of various origins and is associated with metastasis formation and poor prognosis. Bevacizumab, a recombinant humanised monoclonal antibody developed against VEGF, binds to soluble VEGF, preventing receptor binding and inhibiting endothelial cell proliferation and vessel formation. Pre-clinical and clinical studies have shown that bevacizumab alone or in combination with a cytotoxic agent decreases tumour growth and increases median survival time and time to tumour progression. Bevacizumab is the first anti-angiogenetic treatment approved by the American Food and Drug Administration in the first-line treatment of metastatic colorectal cancer. It has shown preliminary evidence of efficacy for breast, non-small-cell lung, pancreatic, prostate, head and neck and renal cancer as well as haematological malignancies. Common toxicities associated with bevacizumab include hypertension, proteinuria, bleeding episodes and thrombotic events. This review summarises the critical role of VEGF and discusses the data available on bevacizumab, from the humanisation of its parent murine monoclonal antibody (mAb) A.4.6.1 to its use in cancer clinical trials.
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PMID:Vascular endothelial growth factor (VEGF) as a target of bevacizumab in cancer: from the biology to the clinic. 1684 97

11Beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) deficiency causes sodium retention and severe hypertension by allowing glucocorticoids access to the non-selective mineralocorticosteroid receptor. Understanding regulation of the HSD11B2 gene is thus of fundamental importance in hypertension research. A number of studies have suggested that second messenger pathways may be important in this regard. In the present study we show that HSD11B2 expression in human renal epithelial P58 cells is regulated at the mRNA and protein level, and that protein kinases A (PKA) and C (PKC) are involved in this process. PKA stimulation resulted in almost two-fold increase while PKC activation in almost two-fold decrease in the HSD11B2 mRNA and protein level. Western blot analysis revealed a dimeric form of 11beta-HSD2 of about 80kDa. Arginine vasopressin (AVP), acting through the AVP2 receptor, as well as 11beta-HSD2 substrates, corticosterone and dexamethasone, up-regulate HSD11B2 expression, suggesting their role as possible factors affecting blood pressure. We show that the activators of the PKA pathway induce, while activators of PKC pathway repress the expression of HSD11B2 in human renal epithelial cells. AVP, acting via the PKA pathway, might be a physiological stimulator of the HSD11B2 expression. The 11beta-HSD2 substrates, both natural (corticosterone) and synthetic (dexamethasone), might protect the mineralocorticosteroid-target cells against cortisol excess.
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PMID:Arginine vasopressin stimulates 11beta-hydroxysteroid dehydrogenase type 2 expression in the mineralocorticosteroid target cells. 1687 38


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